Combined blockade of early and late activated atrial potassium currents suppresses atrial fibrillation in a pig model of obstructive apnea

Dominik Linz*, Ulrich Schotten, Hans-Ruprecht Neuberger, Michael Boehm, Klaus Wirth

*Corresponding author for this work

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27 Citations (Web of Science)

Abstract

BACKGROUND Negative tracheal pressure (NTP) during tracheal obstruction in obstructive apnea increases vagal tone and causes pronounced shortening of the atrial effective refractory period (AERP), thereby perpetuating atrial fibrillation (AF). The role of different atrial potassium channels under those conditions has not been investigated. OBJECTIVE The purpose of this study was to evaluate the atrial effects of blockade of the late activated potassium current (I-Kr) by sotalol, of blockade of the early activated potassium currents (I-Kur/I-to) by AVE0118, and of the multichannel blocker amiodarone during tracheal occlusions with applied NTP. METHODS Twenty-one pigs were anesthetized, and an endotracheal tube was placed to apply NTP (up to -100 mbar) comparable to clinically observed obstructive sleep apnea for 2 minutes. Right AERP and AF inducibility were measured transvenously by a monophasic action potential recording and stimulation catheter. RESULTS Tracheal occlusion with applied NTP caused pronounced AERP shortening. AF was inducible during all NTP maneuvers. Blockade of I-Kr by sotalol, blockade of I-Kur/I-to by AVE0118, and amiodarone did not affect NTP-induced AERP shortening, although they prolonged the AERP during normal breathing. Atropine given after amiodarone completely inhibited NTP-induced AERP shortening. The combined blockade of I-Kr and I-Kur/I-to by sotalol plus AVE0118, however, attenuated NTP-induced AERP shortening and AF inducibility independent of the order of administration. CONCLUSION The atrial proarrhythmic effect of NTP simulating obstructive apneas is difficult to inhibit by class III antiarrhythmic drugs. Neither amiodarone nor blockade of I-Kr or I-Kur/I-to attenuated NTP-induced AERP shortening. However, the combined blockade of I-Kur/I-to and I-Kr suppressed NTP-induced AERP shortening.
Original languageEnglish
Pages (from-to)1933-1939
JournalHeart Rhythm
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Obstructive sleep apnea
  • Atrial fibrillation
  • Antiarrhythmia agents
  • Electrophysiology
  • Potassium-channel

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